1. Field of the Invention:
The subject of this invention relates to a method and composition of a non-invasive, topical treatment and prevention of pathological symptoms of the inner ear and labyrinth, in particular of tinnitus, vertigo, lack of balance, and nausea.
2. Discussion of the Background:
It is known that in the majority of cases, persistent tinnitus and vertigo, accompanied by a lack of balance and nausea, are due to a disorder or disease of the organs of the inner ear or of the auditory nerves. Tinnitus may occur both in the low-frequency and in the high-frequency range; in the low-frequency range, it occurs especially in the presence of disorders of the auditory canal and the middle ear, in the high-frequency, mainly in the presence of disorders of the labyrinth. These persistent symptoms have an extremely negative effect on those affected. One characteristic complex of symptoms, which includes tinnitus, vertigo and lack of balance, possibly in association with nystagmus, hearing impairment and vomiting, is seen, for example, in Meniere's disease. The sudden attacks of the symptoms may be attributable to vasomotor disorders of labyrinth vessels or temporary disorders of the secretion and composition of the labyrinthine liquor. Under the influence of permanent tinnitus and impaired hearing, the persons affected often become irritable, they suffer from anxiety, and, in some cases, develop considerable psychosomatic problems as this illness proceeds.
The therapeutic methods used so far to treat these problems are not sufficiently effective. If it is not possible to identify an underlying disease, only symptomatic measures, such as stimulus deprivation, rest and pharmacological sedation, can be taken. The pharmacological principle frequently used for this purpose is the orally administered dimenhydrinate which has a sedative effect. Scopolamine, a parasympatholytic agent, may also be used; however, this agent is primarily used to treat the pathophysiologically associated phenomenon of motion-induced nausea, i.e., kinetosis, which develops on exposure to externally moving objects. This sickness is also known as motion or sea sickness and is associated with vegetative phenomena, mainly with nausea. In systemic therapy, scopolamine is also administered by transdermal route (Y. W. Chien, Novel Drug Delivery Systems, Drugs and the Pharmaceutical Sciences, Vol. 14, 1982, Marcel Decker, New York), which, when compared to the intramuscular administration of scopolamine, results in a lower and more uniform blood concentration in the body. In spite of this, however, the typical undesirable side effects of scopolamine, in particular, impaired vision, very dry mouth, changes in the ability to concentrate, and somnolence, are observed. The undesirable side effect mentioned last is, among other things, also present after an oral administration of dimenhydrinate which is also used to treat kinetoses but which is less effective. Thus, overall, the administration of scopolamine as a therapeutic principle is very restricted indeed.
In contrast, the appropriate use of local anesthetics in low doses represents a more effective pharmacological approach. A systemic administration, however, is generally possible by means of injection which as such is undesirable and which, in addition, cannot be used due to the fact that it poses the risk of a systemic overdose with serious cardiac side effects. A direct administration by injection or liquid infusion of local anesthetics to the labyrinthine apparatus of the inner ear itself is technically practically impossible; furthermore, this would carry the risk of ototoxic effects.
The pharmacological mechanism of action of local amide and ester anesthetics, e.g., amide-type lidocaine, is to inhibit the rapid sodium ion influx into the fibers of the nerves. In this manner, these anesthetics block the conduction of impulses of the nerve path, which basically includes all regional nerve fibers. Due to their morphology, however, the thinner sensory fibers are more sensitive than motor fibers, which makes it possible to differentiate between various effects. It is also known that intravenous injections of higher doses of lidocaine (T. Gejrot, Atl. Lokalanasthesie Atlas of Local Anesthesia!, pp. 151-152, Thieme, Stuttgart 1970) as well as a blockage of the ganglion cervicothoracicum with procaine have positive effects on the symptoms of Meniere's disease, although these persist only for a limited period of time.
So far, a non-invasive method and composition for the treatment and prevention of pathological symptoms of the inner ear or labyrinth using a topical carrier system has neither been carried out nor described.
The use of topical carrier systems for drug delivery has been reported (see, for example, U.S. Pat. No. 4,765,986 and European Patent No. 0,205,974).
It is known that medicinal effects can be obtained with medicinal plasters or so-called therapeutic plaster systems, designated lately as transdermal therapeutic systems. At present, this type of system is used in connection with the drug scopolamine for kinetosis, nitroglycerine for coronary heart disease and clonidine for hypertension, as well as for transdermally administered estrogens.
Such plaster systems entail diffusion units in which the medications are released by diffusion at controlled rates from a mechanically fixed drug reservoir, usually tissue tolerant polymers. The systems used are currently divided into membrane systems, i.e., membrane plaster and matrix systems. In the membrane systems the drug, after release from the carrier substance, must permeate a membrane, which serves as a control element for the constant absorption rate. Thereby, it is possible to attain a release characteristic, which approximately corresponds to pharmacokinetics of zero order. In matrix systems, the drug stored in depot form diffuses directly from the polymer matrix into the skin.
However, a non-invasive method and composition for the treatment and prevention of pathological symptoms of the inner ear or labyrinth with a periauricularly administered topical carrier system has neither been carried out nor described.